netupitant and Neoplasms
netupitant has been researched along with Neoplasms* in 9 studies
Reviews
3 review(s) available for netupitant and Neoplasms
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Review of oral fixed-dose combination netupitant and palonosetron (NEPA) for the treatment of chemotherapy-induced nausea and vomiting.
Current guidelines recommend the combination of a neurokinin-1 (NK1) receptor antagonist (RA) and a 5-hydroxytryptamine-3 (5-HT3) RA, together with corticosteroids, in order to prevent chemotherapy-induced nausea and vomiting with anthracycline-cyclophosphamide and highly emetogenic chemotherapy, and it is to be considered with moderately emetogenic chemotherapy. Netupitant and palonosetron (NEPA) is a fixed-dose combination of netupitant, a novel, highly selective NK1 RA, and palonosetron, a new-generation 5-HT3 RA, targeting two major emetic pathways in a single oral capsule. In clinical trials, NEPA administered on day 1 together with dexamethasone was highly effective and well tolerated in the prevention of chemotherapy-induced nausea and vomiting in patients with solid tumors undergoing moderately emetogenic chemotherapy or highly emetogenic chemotherapy. NEPA offers maximal convenience, and as a simple guideline-based regimen, has the potential to improve adherence to guidelines. Topics: Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Drug Combinations; Drug Interactions; Humans; Isoquinolines; Nausea; Neoplasms; Palonosetron; Pyridines; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Treatment Outcome; Vomiting | 2015 |
Profile of netupitant/palonosetron (NEPA) fixed dose combination and its potential in the treatment of chemotherapy-induced nausea and vomiting (CINV).
Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors significantly influence CINV. The use of a combination of a 5-hydroxytryptamine-3 (5-HT3) receptor antagonists, dexamethasone, and a neurokinin-1 (NK-1) receptor antagonist has significantly improved the control of acute and delayed emesis in single-day chemotherapy. Palonosetron, a second generation 5-HT3 receptor antagonist with a different half-life, different binding capacity, and a different mechanism of action than the first generation 5-HT3 receptor antagonists, appears to be the most effective agent in its class. Netupitant, is a new NK-1 receptor antagonist with a high binding affinity, a long half-life of 90 hours, is metabolized by CYP3A4, and is an inhibitor of CYP3A4. NEPA is an oral fixed-dose combination of netupitant and palonosetron which has recently been employed in Phase II and Phase III clinical trials for the prevention of CINV in patients receiving moderately and highly emetogenic chemotherapy (MEC and HEC). The clinical trials demonstrated that NEPA (300 mg of netupitant plus 0.50 mg of palonosetron) significantly improved the prevention of CINV compared to the use of palonosetron alone in patients receiving either HEC or MEC. The clinical efficacy was maintained over multiple cycles of chemotherapy. NEPA (Akynzeo(®)) has recently been approved by the Food and Drug Administration (FDA) to treat nausea and vomiting in patients undergoing cancer chemotherapy. Topics: Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Humans; Isoquinolines; Molecular Structure; Nausea; Neoplasms; Palonosetron; Pyridines; Quinuclidines; Vomiting | 2015 |
Emerging treatments in chemotherapy-induced nausea and vomiting.
Chemotherapy-induced nausea and vomiting (CINV) is a concern for many cancer patients. It can have an enormous impact on quality of life. CINV occurring in the first 24 hours after treatment is considered acute, and CINV occurring on days 2 through 5 after treatment is considered delayed. Anticipatory nausea and depression can also occur when patients are reminded of their chemotherapy treatment. CINV can lead to weight changes, fatigue, and the need for additional medications. Even mild to moderate CINV can increase health care utilization and costs, as well as delay treatment. Nausea and vomiting are separate events, although their mechanisms are entwined. Drugs that stop vomiting do not necessarily treat nausea. Control of CINV allows patients to complete treatment and to minimize use of health care resources and additional medications. Current antiemesis agents, such as 5-hydroxytryptamine-3 (5-HT3) antagonists and neurokinin-1 (NK-1) antagonists, have markedly decreased hospitalization for chemotherapy and have nearly eliminated acute emesis. The second-generation 5-HT3 receptor palonosetron has a unique pharmacology that makes it especially effective at preventing delayed emesis. Topics: Allosteric Regulation; Antiemetics; Antineoplastic Agents; Humans; Isoquinolines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Palonosetron; Pyridines; Quinuclidines; Receptors, Serotonin, 5-HT3; Serotonin; Serotonin 5-HT3 Receptor Antagonists; Vomiting | 2013 |
Trials
4 trial(s) available for netupitant and Neoplasms
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Fixed-Dose Netupitant and Palonosetron for Chronic Nausea in Cancer Patients: A Double-Blind, Placebo Run-in Pilot Randomized Clinical Trial.
No clinical trials have examined the effect of netupitant/palonosetron (NEPA) on chronic nausea in patients with cancer.. In this pilot randomized trial, we assessed the efficacy of NEPA and placebo on chronic nausea.. This double-blind, parallel, randomized trial enrolled patients with cancer and chronic nausea for at least 1 month, intensity ≥4/10 and not on moderately or highly emetogenic systemic therapies. Patients started with a placebo run-in period from days 1 to 5; those without a placebo response proceeded to the double-blinded phase between days 6 to 15 (NEPA: placebo 2:1 ratio). The primary outcome was within-group change in average nausea over the 24 hours on a 0-10 numeric rating scale between day 5 and 15.. Among the 53 enrolled patients, 46 proceeded to placebo run-in and 33 had blinded treatment (22 NEPA and 11 placebo). We observed a statistically significant within-group improvement in nausea numeric rating scale between day 5 and 15 in the NEPA group (mean change, -2.0; 95% CI, -3.1 to -0.8) and the placebo group (mean change, -2.3; 95% CI, -3.9 to -0.7). A complete response was achieved in 8 (38%) patients in the NEPA group and 2 (20%) in the placebo group by day 15. No grade 3-4 toxicities were attributed to NEPA. There were no statistically significant between-group differences for the primary/secondary outcomes.. NEPA and placebo were associated with similar magnitude of within-group improvement in chronic nausea without significant between-group differences (Clinicaltrials.gov NCT03040726). Topics: Antiemetics; Antineoplastic Agents; Double-Blind Method; Drug Combinations; Humans; Isoquinolines; Nausea; Neoplasms; Palonosetron; Pilot Projects; Pyridines; Quinuclidines; Vomiting | 2021 |
Phase III safety study of intravenous NEPA: a novel fixed antiemetic combination of fosnetupitant and palonosetron in patients receiving highly emetogenic chemotherapy.
NEPA, an oral fixed combination of the NK1RA netupitant (300 mg) and clinically/pharmacologically distinct 5-HT3RA palonosetron (PALO, 0.50 mg), is the first fixed antiemetic combination to have been approved. A single oral NEPA capsule plus dexamethasone (DEX) given before anthracycline-cyclophosphamide (AC) and non-AC highly emetogenic chemotherapy (HEC) showed superior prevention of chemotherapy-induced nausea and vomiting (CINV) over PALO plus DEX for 5 days postchemotherapy. The safety of NEPA was well-established in the phase II/III clinical program in 1169 NEPA-treated patients. An intravenous (i.v.) formulation of the NEPA combination (fosnetupitant 235 mg plus PALO 0.25 mg) has been developed.. This randomized, multinational, double-blind, stratified (by sex and country) phase III study (NCT02517021) in chemotherapy-naïve patients with solid tumors assessed the safety of a single dose of i.v. NEPA infused over 30 min before initial and repeated cycles of HEC. Patients received either i.v. NEPA or oral NEPA, both with oral DEX on days 1-4. Safety was assessed primarily by treatment-emergent adverse events (AEs) and electrocardiograms.. A total of 404 patients completed 1312 cycles. The incidence and type of treatment-emergent AEs were similar for both treatment groups with the majority of AEs as mild/moderate in intensity. There was no increased incidence of AEs in subsequent cycles in either group. The incidence of treatment-related AEs was similar and relatively low in both groups (12.8% i.v. NEPA and 11.4% oral NEPA during the entire study), with constipation being the most common (6.4% i.v. NEPA, 6.0% oral NEPA). No serious treatment-related AEs occurred in either group. No infusion site or anaphylactic reactions related to i.v. NEPA occurred. No clinically relevant changes in QTc and no cardiac safety concerns were observed.. Intravenous NEPA was well-tolerated with a similar safety profile to oral NEPA in patients with various solid tumors receiving HEC. Topics: Administration, Intravenous; Anthracyclines; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Induction Chemotherapy; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Prognosis; Pyridines; Survival Rate; Vomiting | 2018 |
NEPA, a fixed oral combination of netupitant and palonosetron, improves control of chemotherapy-induced nausea and vomiting (CINV) over multiple cycles of chemotherapy: results of a randomized, double-blind, phase 3 trial versus oral palonosetron.
This study is a multinational, double-blind study comparing a single oral dose of NEPA vs oral PALO in chemotherapy-naïve patients receiving anthracycline/cyclophosphamide-based chemotherapy along with dexamethasone 12 mg (NEPA) or 20 mg (PALO) on day 1. The primary efficacy endpoint was delayed (25-120 h) complete response (CR: no emesis, no rescue medication) in cycle 1. Sustained efficacy was evaluated during the multicycle extension by calculating the proportion of patients with overall (0-120 h) CR in cycles 2-4 and by assessing the probability of sustained CR over multiple cycles.. Of 1455 patients randomized, 1286 (88 %) participated in the multiple-cycle extension for a total of 5969 cycles; 76 % completed ≥4 cycles. The proportion of patients with an overall CR was significantly greater for NEPA than oral PALO for cycles 1-4 (74.3 vs 66.6 %, 80.3 vs 66.7 %, 83.8 vs 70.3 %, and 83.8 vs 74.6 %, respectively; p ≤ 0.001 each cycle). The cumulative percentage of patients with a sustained CR over all 4 cycles was also greater for NEPA (p < 0.0001). NEPA was well tolerated over cycles.. NEPA, a convenient, guideline-consistent, fixed antiemetic combination is effective and safe over multiple cycles of chemotherapy. Topics: Adult; Anthracyclines; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dexamethasone; Double-Blind Method; Female; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Pyridines; Quinuclidines; Vomiting; Young Adult | 2017 |
A phase III study evaluating the safety and efficacy of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting over repeated cycles of chemotherapy.
Safe, effective and convenient antiemetic regimens that preserve benefit over repeated cycles are needed for optimal supportive care during cancer treatment. NEPA, an oral fixed-dose combination of netupitant, a highly selective NK1 receptor antagonist (RA), and palonosetron (PALO), a distinct 5-HT3 RA, was shown to be superior to PALO in preventing chemotherapy-induced nausea and vomiting after a single cycle of highly (HEC) or moderately (MEC) emetogenic chemotherapy in recent trials. This study was designed primarily to assess the safety but also to evaluate the efficacy of NEPA over multiple cycles of HEC and MEC.. This multinational, double-blind, randomized phase III study (NCT01376297) in 413 chemotherapy-naïve patients evaluated a single oral dose of NEPA (NETU 300 mg + PALO 0.50 mg) given on day 1 with oral dexamethasone (DEX). An oral 3-day aprepitant (APR) regimen + PALO + DEX was included as a control (3:1 NEPA:APR randomization). In HEC, DEX was administered on days 1-4 and in MEC on day 1. Safety was assessed primarily by adverse events (AEs), including cardiac AEs; efficacy by complete response (CR: no emesis, no rescue).. Patients completed 1961 total chemotherapy cycles (76% MEC, 24% HEC) with 75% completing ≥4 cycles. The incidence/type of AEs was comparable for both groups. Most frequent NEPA-related AEs included constipation (3.6%) and headache (1.0%); there was no indication of increasing AEs over multiple cycles. The majority of AEs were mild/moderate and there were no cardiac safety concerns based on AEs and electrocardiograms. The overall (0-120 h) CR rates in cycle 1 were 81% and 76% for NEPA and APR + PALO, respectively, and antiemetic efficacy was maintained over repeated cycles.. NEPA, a convenient single oral dose antiemetic targeting dual pathways, was safe, well tolerated and highly effective over multiple cycles of HEC/MEC. Topics: Antineoplastic Agents; Double-Blind Method; Drug Combinations; Humans; Isoquinolines; Nausea; Neoplasms; Palonosetron; Pyridines; Quinuclidines; Vomiting | 2014 |
Other Studies
2 other study(ies) available for netupitant and Neoplasms
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Complementary Pharmacokinetic Profiles of Netupitant and Palonosetron Support the Rationale for Their Oral Fixed Combination for the Prevention of Chemotherapy-Induced Nausea and Vomiting.
NEPA is the first fixed-combination antiemetic composed of the neurokinin-1 receptor antagonist netupitant (netupitant; 300 mg) and the 5-hydroxytryptamine-3 receptor antagonist palonosetron (palonosetron; 0.50 mg). This study evaluated the pharmacokinetic profiles of netupitant and palonosetron. The pharmacokinetic profiles of both drugs were summarized using data from phase 1-3 clinical trials. netupitant and palonosetron have high absolute bioavailability (63%-87% and 97%, respectively). Their overall systemic exposures and maximum plasma concentrations are similar under fed and fasting conditions. netupitant binds to plasma proteins in a high degree (>99%), whereas palonosetron binds to a low extent (62%). Both drugs have large volumes of distribution (cancer patients: 1656-2257 L and 483-679 L, respectively). netupitant is metabolized by cytochrome P450 3A4 to 3 major pharmacologically active metabolites (M1, M2, and M3). palonosetron is metabolized by cytochrome P450 2D6 to 2 major substantially inactive metabolites (M4 and M9). Both drugs have similar intermediate-to-low systemic clearances and long half-lives (cancer patients: netupitant, 19.5-20.8 L/h and 56.0-93.8 hours; palonosetron: 7.0-11.3 L/h and 43.8-65.7 hours, respectively). netupitant and its metabolites are eliminated via the hepatic/biliary route (87% of the administered dose), whereas palonosetron and its metabolites are mainly eliminated via the kidneys (85%-93%). Altogether, these data explain the lack of pharmacokinetic interactions between netupitant and palonosetron at absorption, binding, metabolic, or excretory level, thus highlighting their compatibility as the oral fixed combination NEPA, with administration convenience that may reduce dosing mistakes and increase treatment compliance. Topics: Antiemetics; Antineoplastic Agents; Biological Availability; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Drug Combinations; Humans; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Palonosetron; Pyridines; Vomiting | 2019 |
Preventing chemotherapy-induced nausea and vomiting with netupitant/palonosetron, the first fixed combination antiemetic: current and future perspective.
Chemotherapy-induced nausea and vomiting (CINV) can be prevented in most patients receiving appropriate antiemetic treatment. However, inadequate uptake of current antiemetic guideline recommendations by physicians, and poor treatment adherence by patients, lead to suboptimal CINV control. There is an unmet need to optimize guideline-consistent use of antiemetics to improve CINV management and prevention. Herein, we provide an overview of CINV, then discuss oral and intravenous NEPA, the first fixed combination antiemetic, composed of netupitant/fosnetupitant and palonosetron. We describe the main pharmacologic and pharmacokinetic characteristics of NEPA, and review the clinical evidence supporting its use in the prevention of CINV. Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Humans; Nausea; Neoplasms; Palonosetron; Practice Guidelines as Topic; Prognosis; Pyridines; Vomiting | 2019 |